Imaging sciences are not at a stage in which in vivo imaging can occur at near mum resolutions with image specificity at the physiological, cellular and molecular level. Although the molecular basis of many diseases are well defined, we do not have a full understanding of the mechanism by which they develop in vivo nor have we fully harnessed the potential for translating advances in molecular sciences into clinical practice imaging. Increased understanding of these areas and development of novel techniques is likely to provide new important directions in the earlier detection, molecular characterization and treatment of cancers. The proposed program at the Center for Molecular Imaging Research (CMIR) at Massachusetts General Hospital (MGH), Harvard Medial School, is organized to attack fundamental imaging at the cellular and molecular level. The principal research projects address imaging of specific enzymes in intact cellular and molecular level. The principal research projects address imaging of specific enzymes in intact tumor environments using smart optical probes (PI: R. Weissleder), in vivo imaging of angiogenesis and novel anti-angiogenic treatments (PI: a. Bogdanov), in vivo imaging of gene expression using new vectors and imaging of gene expression using new vectors and imaging marker gene S(PI: X.O. Breakefield) and in vivo tracking of progenitor and hematopoietic cells (PI: D.T. Scadden). These studies will be complemented by pilot projects dealing with viral delivery to tumors, developing high efficiency internalizing receptors for imaging probes, novel optical tomography systems for interrogating deep seated tumors and intracellular targeting and strategies for targeting of imaging probes to different intracellular components. The program also includes two scientific resources (a chemistry resource for the synthesis of a molecular imaging probes and a small animal imaging resource), a pilot project program and a career development program for multi-disciplinary training of scientists. A major goal of the Center in the long-term is the multi- disciplinary research approach and interaction with and involvement of basic research groups in the Harvard and other national medical areas, largely through collaborative experiments utilizing the core resources. The Center will thus serve as a regional and national resource to move research in the field ahead and recruit new investigators into molecular imaging research.